For a long time, agar is a representative seaweed-derived polysaccharide which is widely used for food additives, medicines, cosmetics, livestock feed, and industrial raw materials. The agar is one of comparatively abundant fishery resources, and its yield is about 3,600 tons per year in Korea. However, only a portion of the total yield is simply processed in actual practice to be merely used as a cheap raw material, and the rest of the total yield went by wayside so that the added value is very low compared to the natural resource amount. Accordingly, there is great demand for development of a novel use of the abundant Korean agar or a study for the added value enhancement.
The agar consists of agarose and agaropectin. The agarose is formed in a straight chain structure linked by α-1,3 bond, which is obtained by repeating agarobiose which is a monomer in which D-galactose and 3,6-anhydro-L-galactose are linked in β-1,4 bond so that the agarose's gel power is strong. On the other hand, the agaropectin is essentially composed of agarobiose units like agarose, but includes acidic group such as sulfuric acidic group so that the gel power thereof is weak.
Among them, the agarose is digested into neoagarobiose via neoagarotetraose by β-agarase acting on β-1,4 bonds, and subsequently, is finally digested into D-galactose and 3,6-anhydro-L-galactose by α-agarase acting on the α-1, 3 bond.
Meanwhile, Streptomyces coelicolor A3 (2), actinomycetes, is known to produce an extracellular agarase (which is secreted out of cells) that digests agar (Stanier et al., 1942, J. Bacteriol.; Hodgson and Chater, 1981, J. Gen. Microbiol.). The agarase is encoded by a dagA gene. The dagA gene is a beta-agarase gene whose function is the only known in actinomycetes and plays an important role in the studies on agarase production in actinomycetes. In particular, the Streptomyces coelicolor is the most widely used strain for the molecular biological study on actinomycetes, and the sequence of chromosomal DNA was analyzed and disclosed in the Sanger center in England in 2002.
Meanwhile, sepsis is an inflammatory reaction induced when a pathogenic gram-negative bacterium infects a living body so that a lipopolysaccharide (LPS), a component of a cell wall, acts as a toxin to result in excessive activation of an immune system of a living body. Further, sepsis may cause infectious disease in the whole body or result in a shock when symptoms are severe. Specifically, sepsis is mainly occurred when patients with underlying diseases such as malignant tumor, leukemia, malignant lymphoma, acquired immunodeficiency syndrome (AIDS), collagen disease, renal failure, liver disease, cerebrovascular disorder, diabetes or hosts with humoral immunodeficiency or cellular immunodeficiency, whose resistance is weak, such as senior and premature infant, are subject to chemotherapy of adrenal steroids or anti-neoplastic, radiation therapy such as cobalt irradiation, or treatment and surgery such as indwelling catheter, hemodialysis, organ transplantation, and cardiac disease. Sepsis is a very serious disease with a mortality rate of more than 30%, which is the main cause of death of patients hospitalized in an intensive care unit. Despite medical technology's advance, many cases of sepsis occur still due to post-operative infection in worldwide, and many cases of sepsis occur when a person with weak immunity of the body, such as neonates or seniors, is infected. Typically, the birth sepsis is known to develop in about 3 of 1,000 mature infants, but premature infants are known to increase the attack rate by 3 to 4 times. When a patient has sepsis, the patient is usually treated with antibiotics. However, when microorganisms are proliferated since the suitable treatment is delayed, or when the infection is caused by a strain resistant to antibiotics, antibiotics only may not effectively treat the disease, and the number of pathogens resistant to various antibiotics is increasing. Thus, it is urgently needed to develop a novel therapeutic agent for sepsis
The inventors of the present invention have extensively studied to meet the requirements. As a result, the inventors have found that agar-derived neoagarooligosaccharide prepared by the DagA enzyme reaction has excellent effects that not only inhibits the growth of bacteria, but also eliminates the endotoxin isolated from dead bacteria. Thus, it is used in combination with antibiotics so as to minimize the side effects caused by antibiotics and to have remarkably excellent effects of treating sepsis compared to the single administration therewith, thereby completing the present invention.